Itch is a common clinical problem that is often difficult to treat. There is currently little understanding of the mechanism used in the CNS to produce itch and this likely contributes to the inability to treat itch. In recent years it have become cler that information related to itch is carried in the periphery and spinal cord by neurons that are also activated by noxious stimuli. This suggests that information necessary for the production of itch in the brain must be extracted from the responses of polysensory neurons in a process called decoding. The proposed studies, will for the first time, use single unit electrophysiologica techniques to determine the areas in the thalamus and cortex where processing of pruriceptive information occurs. The responses of single neurons in the thalamus to various itch-and pain-producing stimuli will be determined. The cortical areas to which pruriceptive thalamic neurons project will be determined using antidromic activation methods. In addition, responses of individual cortical neurons to pruritogens and pain-producing stimuli will be determined. The proposed studies will determine the thalamic nuclei and cortical areas in which processing of information related to itch and pain occur. In addition, using a Machine Learning approach, we will determine the contributions of the intensity and pattern of action potentials within responses to differential coding of itch and pain related responses. The proposed studies will considerably expand our understanding of the CNS mechanisms that produce itch and pain. RELEVANCE: Very little is known about the neural systems in the thalamus and cerebral cortex that underlie production of the sensation of itch. This lack of understanding likely contributes to the paucity of effective treatments for the majority of types of chronic itch. The proposed studies will determine the areas in the thalamus and cortex in which single neurons process and transmit information about itch and pain.